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PMID: 21041407 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program.

Genes & development ·Vol. 24 ·No. 21 ·2010-11-01 ·Pages 2383-8

Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D

Abstract

Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.

MeSH Terms
Adaptor Proteins, Signal Transducing/deficiency,genetics,physiology Animals Blotting, Western Cell Cycle Proteins/genetics,metabolism Colonic Polyps/chemically induced,genetics,physiopathology Dextran Sulfate Drosophila Proteins/genetics,metabolism Female Gene Expression Humans Immunohistochemistry Intestinal Mucosa/metabolism Intestines/pathology,physiopathology Intracellular Signaling Peptides and Proteins/genetics,metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Phosphoproteins/deficiency,genetics,physiology Protein Serine-Threonine Kinases/genetics,metabolism RNA, Messenger/genetics,metabolism Regeneration/genetics,physiology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction/genetics,physiology YAP-Signaling Proteins
Chemicals
Adaptor Proteins, Signal Transducing Cell Cycle Proteins Drosophila Proteins Intracellular Signaling Peptides and Proteins Phosphoproteins RNA, Messenger Sav1 protein, mouse YAP-Signaling Proteins Yap1 protein, mouse Dextran Sulfate Protein Serine-Threonine Kinases hpo protein, Drosophila
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cai Jing
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Zhang Nailing
Zheng Yonggang
de Wilde Roeland F
Maitra Anirban
Pan Duojia
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1978810
Published
2010-11-01
Pages
2383-8
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2964748
Subset
IM
Grants
NCI NIH HHS · R01 CA134767 · United States
NCI NIH HHS · R01CA134767 · United States
NCI NIH HHS · R01CA113669 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · P01 CA134292 · United States
NCI NIH HHS · R01 CA113669 · United States
NCI NIH HHS · P01CA134292 · United States
Corrections
CommentIn
PMID: 21155175
External Links
PubMed source DOI: 10.1101/gad.1978810 PMC Full Text View journal details
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